title: Recombinant human arginase induced caspase-dependent apoptosis and autophagy in non-Hodgkin's lymphoma cells.
abstract: Arginase, an arginine-degrading enzyme, has gained increased attention recently as a new experimental therapeutics for a variety of malignant solid cancers. In this study, we found that recombinant human arginase (rhArg) could induce remarkable growth inhibition, cell cycle arrest, and caspase-dependent apoptosis in Raji and Daudi non-Hodgkin's lymphoma (NHL) cells through arginine deprivation. Interestingly, rhArg-treatment resulted in the appearance of autophagosomes and upregulation of microtubule-associated protein light chain 3 II, indicating that rhArg induced autophagy in lymphoma cells. Further study suggested that mammalian target of rapamycin/S6k signaling pathway may be involved in rhArg-induced autophagy in NHL cells. Moreover, blocking autophagy using pharmacological inhibitors (3-methyladenine and chloroquine) or genetic approaches (small interfering RNA targeting autophagy-related gene 5 and Beclin-1) enhanced the cell killing effect of rhArg. These results demonstrated that rhArg has a potent anti-lymphoma activity, which could be improved by in combination with autophagic inhibitors, suggesting that rhArg, either alone or in combination with autophagic inhibitors, could be a potential novel therapeutics for the treatment of NHL.
authors.affiliation: Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: X
authors.initials: X
authors.lastname: Zeng
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Fan
authors.forename: H
authors.initials: H
authors.lastname: Zhao
authors.forename: Z
authors.initials: Z
authors.lastname: Xian
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Ju
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001119:Arginase / Q000494:pharmacology* / Q000627:therapeutic use*; D001120:Arginine / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D001120:Arginine; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D020169:Caspases; D001119:Arginase